Sugimoto Takashi, Seki Naohiko, Shimizu Satoya, Kikkawa Naoko, Tsukada Jun, Shimada Hideaki, Sasaki Keita, Hanazawa Toyoyuki, Okamoto Yoshitaka, Hata Akira
Department of Functional Genomics, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
Genes Chromosomes Cancer. 2009 Feb;48(2):132-42. doi: 10.1002/gcc.20626.
To identify putative biomarkers in squamous cell carcinoma (SCC), a survey of parallel chromosomal alterations and gene expression studies in 10 SCC cell lines were performed using array-comparative genomic hybridization (CGH) and oligo-microarray techniques. The most frequent changes were gains of 11q13.1-13.3 and losses of 18q12.1-23 in SCC. Furthermore, the expression levels of the sets of genes at both these loci in SCC were measured using microarray analysis. By combining the array-CGH with the microarray data, 10 genes at 11q13.1-13.3 and 6 genes at 18q12.1-23 whose expression correlated with chromosomal alterations were identified. To verify the expression levels of the identified genes, we used expression analysis data derived from our earlier study of clinical specimens. In clinical samples, six genes (GAL, GSTP1, MRPL11, MRPL21, SF3B2, and YIF1A) at 11q13.1-13.3 and one gene (GALR1) at 18q23 showed a significant difference between normal and tumor samples. GAL, coding for the neuropeptide galanin, and GALR1, a galanin receptor, were identified as candidate genes of oncogenesis in SCC. The expression levels of GAL, GALR1, GALR2, and GALR3 were confirmed by real-time PCR. The expression ratio between GAL and GALR1 showed a significant negative correlation. GALR1 is a G-protein-coupled receptor that activates GTP-binding proteins to trigger signaling cascades such as the mitogen-activated protein kinase pathway, and is a well-established mitogenic pathway. This further supports the hypothesis that the genes involved in the GAL signaling cascade are candidates for regulation of oncogenesis in SCC.
为了鉴定鳞状细胞癌（SCC）中的潜在生物标志物，我们使用阵列比较基因组杂交（CGH）和寡核苷酸微阵列技术，对10个SCC细胞系中的平行染色体改变和基因表达进行了研究。SCC中最常见的变化是11q13.1 - 13.3区域的扩增和18q12.1 - 23区域的缺失。此外，通过微阵列分析测量了SCC中这两个位点的基因集的表达水平。通过将阵列CGH与微阵列数据相结合，在11q13.1 - 13.3区域鉴定出10个基因，在18q12.1 - 23区域鉴定出6个基因，其表达与染色体改变相关。为了验证所鉴定基因的表达水平，我们使用了来自我们早期临床标本研究的表达分析数据。在临床样本中，11q13.1 - 13.3区域的6个基因（GAL、GSTP1、MRPL11、MRPL21、SF3B2和YIF1A）以及18q23区域的1个基因（GALR1）在正常样本和肿瘤样本之间显示出显著差异。编码神经肽甘丙肽的GAL和甘丙肽受体GALR1被鉴定为SCC肿瘤发生的候选基因。通过实时PCR证实了GAL、GALR1、GALR2和GALR3的表达水平。GAL和GALR1之间的表达比率显示出显著的负相关。GALR1是一种G蛋白偶联受体，可激活GTP结合蛋白以触发信号级联反应，如丝裂原活化蛋白激酶途径，这是一个公认的促有丝分裂途径。这进一步支持了这样的假设，即参与甘丙肽信号级联反应的基因是SCC肿瘤发生调控的候选基因。
